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Volume 14 Supplement 2

Sepsis 2010

Neonatal LPS exposure reduces stress fever in adult rats: modulation by glucocorticoids and PGE2

Immune challenges during the neonatal period may permanently program immune responses later in life, including endotoxin fever. We tested the hypothesis that neonatal endotoxin exposure affects stress fever in adult rats. In control rats (treated with saline as neonates; nSal) body temperature peaked ~1.5°C during open-field stress, whereas in rats exposed to endotoxin (lipopolysaccharide, LPS) as neonates (nLPS) stress fever was significantly attenuated. Following stress, plasma corticosterone levels significantly increased from 74.29 ± 7.05 ng/ml to 226.29 ± 9.87 ng/ml in nSal rats, and from 83.43 ± 10.31 ng/ml to 324.7 ± 36.87 ng/ml in nLPS rats. Animals treated with LPS as neonates and adrenalectomized 1 week before experimentation no longer displayed the attenuated febrile response to stress. This attenuated stress fever caused by an increased corticosterone secretion is likely to be linked to an inhibitory effect of glucocorticoids on cyclooxygenase activity/PGE2 production in the preoptic/anteroventral third ventricular region (AV3V) since stress failed to cause a significant increase in PGE2 in nLPS rats, and this effect was reverted by adrenalectomy. Altogether, the present results indicate that endogenous glucocorticoids are key modulators of the attenuated stress fever in adults rats treated with LPS as neonates, and they act downregulating PGE2 production. Moreover, our findings also support the notion that neonatal immune stimulus affects programming of stress responses during adulthood, despite the fact that inflammation and stress are two distinct processes mediated largely by different neurobiological mechanisms.


Supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Universidade de São Paulo (USP).

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Correspondence to LGS Branco.

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Branco, L., Soriano, R. Neonatal LPS exposure reduces stress fever in adult rats: modulation by glucocorticoids and PGE2. Crit Care 14, P16 (2010).

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  • Glucocorticoid
  • PGE2
  • Corticosterone
  • Corticosterone Level
  • Plasma Corticosterone